Search PubMed⌕ Search

Biomedical subjects

A Hogan

Publications and source records attributed to A Hogan.

At least 19 recordsLinked to original sources

Polymorphism at the beta-adrenergic receptor (ADRB3) locus of Merino sheep and its association with lamb mortality.

Beta3-adrenergic receptors are predominantly found on the surface of adipocytes and are major mediators of the lipolytic and thermogenic effects of high catecholamine concentrations. Recently, variation in the ovine beta3-adrenergic receptor (ADRB3) gene has been reported to be associated with lamb survival. In this study, polymerase chain reaction-single strand conformational polymorphism analysis of part of the ADRB3 intron was used to genotype 4488 Merino lambs born at 10 farms throughout the South Island of New Zealand. Univariate and multivariate odds ratios for each allele revealed a significant association of the E allele with cdd survival and of the D allele with mortality. This variation at the ADRB3 locus may assist in the genetic selection for survival in Merino sheep.

Animals↗

Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues.

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.

Aged↗

Outcomes after combination photodynamic therapy and immunosuppression for inflammatory subfoveal choroidal neovascularisation.

AIM: To report the visual and angiographic outcomes after combination photodynamic therapy (PDT) and immunosuppression for inflammatory subfoveal choroidal neovascularisation (CNV). METHODS: Retrospective review of six consecutive patients, five female and one male, aged 23-40 years with active subfoveal CNV secondary to posterior uveitis. Patients received either intravitreal triamcinolone or systemic immunosuppression (mycophenolate mofetil, tacrolimus) and PDT. Five patients had intravitreal triamcinolone injections and two patients were on systemic immunosuppression; all patients underwent PDT (mean two treatments). Visual acuity was measured on a 2 metre ETDRS chart and fluorescein angiograms were performed at each visit. RESULTS: Median follow up was 15 months (range 10-31). Vision improved by a median of 13 letters in five patients and remained stable (+/-1 letter) in one patient. Median visual acuity improved from 20/160 at presentation to 20/40 at latest follow up (p=0.03). There was a reduction in clinical exudation and cessation of angiographic leakage in all six patients. All interventions were well tolerated. CONCLUSION: Combination PDT and immunosuppression may be a useful therapeutic option for young patients with active inflammatory subfoveal CNV.

Adult↗

ADAM gene expression and regulation during human osteoclast formation.

In this study, we identified the expression and the regulation of ADAM members (a disintegrin and metalloprotease) at both gene and protein levels during human osteoclast differentiation and activity. Human peripheral blood monocytes (HPBMC) treated with M-CSF and RANKL were used as an in vitro fusion model. In parallel, we used human osteoclastoma (OCL) tumor as a source of mature osteoclasts, and human osteoblastic cells as a control representing nonfusing and non-resorbing bone cells. RT-PCR using ADAM-specific primers enabled us to identify the expression of ADAM 8, 9, 10, 15, 17, and 28 in both osteoclasts and osteoblasts. Using primers specific for each ADAM 12 isoform (L and S), we observed a strong signal for both forms (ADAM 12L and ADAM 12S) in osteoblastic cells, while only ADAM 12S was detectable in HPBMC-derived osteoclasts and osteoclastoma. Gene regulation was studied using real-time PCR analysis performed during HPBMC differentiation; this showed a progressive increase of ADAM 12 mRNA level from day 1 to 8 of the culture, while at around day 9, ADAM 12 mRNA level decreased 2-fold. We also showed that ADAM 8, ADAM 17, and ADAM 28 decreased according to the stage of HPBMC differentiation or fusion. ADAM 10 was unaltered during cell fusion. However, confocal immunolocalization showed that ADAM 10 protein re-localized from the nuclei and cytoplasm to the plasma membrane during culture and to the ruffled border in resorbing cells. The same re-localization process was observed using an ADAM 12S-specific antibody during HPBMC differentiation. Between days 12 and 14, ADAM 12 co-localized with the F-actin ring, and at day 15, a strong signal was also present in ruffled border or sealing zone area of osteoclasts. Our results describe the expression and regulation of various ADAMs in human bone cells and the selective expression of ADAM 12L in osteoblasts. Our gene regulation and protein localization studies suggest a function for ADAM 10 and ADAM 12S in the formation of osteoclasts from HPBMC and resorption activity.

Carrier Proteins↗

Polymorphism at the ovine beta3-adrenergic receptor locus: associations with birth weight, growth rate, carcass composition and cold survival.

The beta3-adrenergic receptors (ADRB3s) are predominantly found on the surface of adipocytes and are the major mediators of the lipolytic and thermogenic effects of high catecholamine concentrations. Polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of part of the ovine beta3-adrenergic receptor gene (ADRB3) intron was used to screen 12 large Merino half-sib families for sequence variation. Six different alleles that segregated in a Mendelian fashion were observed. The genetic basis for the allelic differences were identified by sequencing the ADRB3 (coding and non-coding regions) from animals that were homozygous for each of the alleles. Five sire lines (two Merino x Merino, two Merino x Coopworth, one Dorset Down x Coopworth) provided phenotypic and genotypic data used to ascertain the effects of allelic variation at the ADRB3 locus on birth weight, weaning weight, growth rate (up until weaning), carcass composition at 63 days post-weaning and cold survival. Statistical analyses within each half-sib family showed that in some sire lines (S13, S15, and S17) the inheritance of a particular allele was associated with increased birth weights and/or increased growth rates up until weaning. The inheritance of a particular sire allele was associated with fatter carcasses in sire line S16. Chi-squared analysis revealed the association of the E allele with cold survival and the D allele with cold-related mortality in sire line S14. Such associations support the hypothesis that ADRB3s are involved in energy homeostasis. With more research, the variation detected at the ADRB3 locus may assist in the genetic selection for desirable animal production traits.

Acclimatization↗

The modulation of matrix metalloproteinase and ADAM gene expression in human chondrocytes by interleukin-1 and oncostatin M: a time-course study using real-time quantitative reverse transcription-polymerase chain reaction.

OBJECTIVE: Previous studies have reported elevated levels of interleukin-1 (IL-1) and oncostatin M (OSM) in rheumatoid joints, as well as the synergistic degradation of human articular cartilage by this cytokine combination. The present study was undertaken to investigate the ability of IL-1 and OSM to modulate gene expression of matrix metalloproteinase (MMP), ADAM, and ADAM-TS (ADAM with thrombospondin motifs) family members in human chondrocytes. METHODS: T/C28a4 human chondrocytes were stimulated for 2-48 hours with IL-1 and/or OSM. Total RNA was harvested, reverse transcribed, and assessed by real-time polymerase chain reaction for the expression of various MMP, ADAM, and ADAM-TS messenger RNAs (mRNA). Results were normalized to 18S ribosomal RNA. RESULTS: IL-1 and OSM synergized to markedly induce the expression of the collagenases MMP-1, MMP-8, and MMP-13 as well as MMP-3, an activator of proMMPs. Expression of mRNA for MMPs 1, 3, and 13 was induced early, whereas that of MMP-8 mRNA occurred late. Gene expression of MMP-14, an MMP that degrades collagen and activates proMMP-13, was elevated by this combination. IL-1 and OSM also synergized to induce gene expression of the aggrecanase ADAM-TS4, but not ADAM-TS5. CONCLUSION: These data indicate that the potent cartilage-degrading properties of the combination of IL-1 and OSM are potentially mediated by a synergistic induction of the aggrecan-degrading enzyme ADAM-TS4 and the collagen-degrading enzymes MMP-1, MMP-8, MMP-13, and MMP-14, although differences in the magnitude of response and in the time course of induction were observed. A role for MMPs 3 and 14 in the activation of proMMPs may also be implicated.

Cell Line, Transformed↗

Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions.

Syntrophins are modular adapter proteins that link ion channels and signaling proteins to dystrophin and its homologues. A yeast two-hybrid screen of a human brain cDNA library using the PDZ domain of gamma 1- syntrophin, a recently identified brain-specific isoform, yielded overlapping clones encoding the C terminus of diacylglycerol kinase-zeta (DGK-zeta), an enzyme that converts diacylglycerol into phosphatidic acid. In biochemical assays, the C terminus of DGK-zeta, which contains a consensus PDZ-binding motif, was found to be necessary and sufficient for association with gamma 1-syntrophin. When coexpressed in HeLa cells, DGK-zeta and gamma 1-syntrophin formed a stable complex that partitioned between the cytoplasm and nucleus. DGK-zeta translocates from the cytosol to the nucleus, a process negatively regulated by protein kinase C phosphorylation. We found that DGK-zeta recruits gamma 1-syntrophin into the nucleus and that the PDZ-binding motif is required. Disrupting the interaction altered the intracellular localization of both proteins; DGK-zeta accumulated in the nucleus, whereas gamma 1-syntrophin remained in the cytoplasm. The level of endogenous syntrophins in the nucleus of HeLa cells also reflected the amount of nuclear DGK-zeta. In the brain, DGK-zeta and gamma 1-syntrophin were colocalized in cell bodies and dendrites of cerebellar Purkinjie neurons and other neuronal cell types, suggesting that their interaction is physiologically relevant. Moreover, coimmunoprecipitation and pull-down experiments from brain extracts and cells suggest that DGK-zeta, gamma 1-syntrophin, and dystrophin form a ternary complex. Collectively, our results suggest that gamma 1-syntrophin participates in regulating the subcellular localization of DGK-zeta to ensure correct termination of diacylglycerol signaling.

Adaptor Proteins, Signal Transducing↗

What is the most cost-effective way to identify silica problem worksites?

BACKGROUND: State based surveillance systems to identify cases of silicosis have been developed over the past 18 years to target worksite interventions to reduce the incidence of silicosis. Using data from the Michigan silicosis surveillance system, we conducted an analysis to determine the most cost-effective way to identify problem worksites. METHODS: The initial reporting source of all 470 confirmed cases of silicosis reported to the Michigan surveillance system from 1989 to 1995 was identified. The cost of identifying confirmed cases, worksites, problem worksites, silica problem worksites, and the number of current silica-exposed workers was determined for four reporting sources: hospitals; physicians; workers' compensations; and death certificates. RESULTS: Hospital reports were the first to identify 67% of the confirmed cases, 74% of the worksites, and 58% of the problem worksites. Physician reports initially identified 17% of confirmed cases, 15% of worksites, and 26% of problem worksites. Workers' compensation records initially identified 11% of confirmed cases, 4% of worksites, and 8% of problem worksites. Death certificates initially identified 5% of confirmed cases, 7% of worksites, and 8% of problem worksites. Hospital reports were the most cost-effective way to identify cases (US$ 143), worksites (US$ 313), and problem worksites (US$ 454). CONCLUSIONS: Hospital discharge records identified the greatest number of confirmed cases and problem worksites and was the most cost-effective approach to identify both individuals with silicosis and worksites with problems.

Cost-Benefit Analysis↗

Health promotion needs of young people with disabilities--a population study.

PURPOSE: Few research studies have sought to examine the health promotion needs of young people with disabilities. This paper reports the association between self-reported disability and various health behaviours (tobacco and alcohol use, physical activity, sedentary activities) psycho-social outcomes and school satisfaction. METHOD: Cluster stratified random sampling was combined with a cross-sectional descriptive design to obtain 3918 school students attending year 6 (primary school), year 8 and year 10 (high school) throughout New South Wales (Australia), to complete a self-administered questionnaire. RESULTS: The prevalence of self-reported disability among this student sample was 5.8%. The most frequently reported disabilities were physical, sensory and learning disabilities. Students with disabilities reported similar health and educational outcomes as their able-bodied peers. However, they also reported lower levels of school satisfaction, greater voluntary absenteeism and were more likely to get drunk or smoke cigarettes. Students with disabilities reported higher levels of psycho-social distress. They were also as physically active as other students, but also spent more time engaged in sedentary activities. CONCLUSION: Students with self-reported disabilities exhibit attitudes and behaviours that are consistent with studies of students who are alienated from their school communities. Community-based health promotion interventions are required to address these issues in order to prevent the onset of secondary disease processes or additional disability.

Adolescent↗

Outcome after ischaemic stroke in childhood.

A parental questionnaire was used to investigate the outcome for children who had had ischaemic stroke, who were seen at Great Ormond Street Hospital, London between 1990 and 1996. The results of functional assessments carried out by a physiotherapist and an occupational therapist, and of quantitative evaluations carried out by a neuropsychologist were used for validation where possible. The relationship between clinical and radiological factors and outcome were examined. The children were aged between 3 months and 15 years at the time of stroke (median age 5 years) and the period of follow-up ranged from 3 months to 13 years (median duration 3 years). Of the 90 children for whom data were obtained, 13 (14%) had no residual impairments. Outcome was good in 37 children (40%) and poor in 53 (60%) (defined according to whether impairments interfered with daily life). Agreement, as measured by Cohen's kappa, was good or very good between the parents' responses and the qualitative measures provided by the medical professionals and the therapists, but only fair to moderate for the quantitative measures provided by the neuropsychologists. This may reflect different parental perceptions of the physical and cognitive aspects of outcome. Younger age at time of the stroke was the only significant predictor of adverse outcome.

Adolescent↗

Why most workers with occupational repetitive trauma do not file for workers' compensation.

Despite the availability of no fault insurance for wage replacement and medical care costs, the majority of workers diagnosed with an occupational disease do not apply for workers' compensation. The objective of the study was to determine the reasons why workers diagnosed with work-related musculoskeletal disease did not apply for workers' compensation benefits. A cross-sectional study of 1598 individuals diagnosed with neck, upper extremity, and low back work-related musculoskeletal disease from April to June 1996 was performed. All individuals were interviewed over the telephone using a standardized questionnaire. The questionnaire included questions about the precipitating event; demographics; health limitations; mood; pain level; and attitudes toward their health care provider, fellow workers, management, work environment, and filing for workers' compensation. Whenever possible, standardized questions from previous surveys were used. The interviewed individuals with work-related musculoskeletal disease were reported by health care practitioners as required by the state of Michigan's occupational disease reporting law. Workers reported during 12 weeks in the spring of 1996 by a Michigan health care professional as having a neck, back, or upper extremity musculoskeletal disorder were eligible to participate. Among the 2703 reports received, 490 individuals could not be reached, 22 did not speak English, 12 had died or were too incapacitated by other medical conditions, and 581 refused. We interviewed 59% of all eligible workers and 73% of all workers who were reachable and capable of responding in English. Only 25% of workers diagnosed with musculoskeletal disease filed a workers' compensation claim. The factors significantly associated with filing a claim were (1) increased length of employment (> 21 years: odds ratio [OR], 3.01, 95% confidence interval [CI], 1.31 to 6.90); 11 to 20 years: OR, 2.34, 95% CI, 1.01 to 5.47; 6 to 10 years: OR, 1.76, 95% CI, 0.73 to 4.25; 1 to 5 years: OR, 2.36, 95% CI, 1.03 to 5.42; < 1 year: OR, 1.00; (2) lower annual income (< $40,000: OR, 1.75, 95% CI, 1.06 to 2.88 vs > or = $80,000: OR, 1.00); (3) workers' dissatisfaction with coworkers (OR, 1.76, 95% CI, 1.01 to 3.06); (4) physician restrictions on activity (OR, 2.16, 95% CI, 1.55 to 3.00); (5) type of physician providing treatment (specialist, including surgeon or orthopedist: OR, 3.63, 95% CI, 2.37 to 5.55); physical and occupational therapist: OR, 2.15, 95% CI, 1.35 to 3.43); family practitioner: OR, 1.33, 95% CI = 0.89 to 2.01; company physician: OR = 1.00); (6) off work > or = 7 days (OR, 14.85, 95% CI, 10.57 to 20.85); (7) decreased current health status (OR, 0.82, 95% CI, 0.70 to 0.96); and (8) increased severity of illness (OR, 1.24, 95% CI, 1.06 to 20.88). This study showed that only 25% of workers with a work-related musculoskeletal condition filed for workers' compensation and refutes the common perception that an individual with a work-related problem is likely to file a workers' compensation claim. The strongest predictors of who would file were those factors associated with the severity of the condition. Other factors were increasing length of employment, lower annual income, and worker dissatisfaction with coworkers. Our study population consisted mainly of unionized autoworkers, and our findings may not be generalizable to the total workforce.

Adolescent↗

Blue babies and nitrate-contaminated well water.

The use of nitrate-contaminated drinking water to prepare infant formula is a well-known risk factor for infant methemoglobinemia. Affected infants develop a peculiar blue-gray skin color and may become irritable or lethargic, depending on the severity of their condition. The condition can progress rapidly to cause coma and death if it is not recognized and treated appropriately. Two cases of blue baby syndrome were recently investigated. Both cases involved infants who became ill after being fed formula that was reconstituted with water from private wells. Water samples collected from these wells during the infants' illnesses contained nitrate-nitrogen concentrations of 22.9 and 27.4 mg/L.

Environmental Exposure↗

Investigation of a cluster of leukaemia in the Illawarra region of New South Wales, 1989-1996.

OBJECTIVES: To investigate a cluster of leukaemia among young people and assess the plausibility of a disease-exposure relationship. DESIGN: Descriptive analysis of population-based leukaemia incidence data, review of evidence related to the causation of leukaemia, assessment of environmental exposures to known leukaemogens, and resulting risks of leukaemia. SETTING: Illawarra region of New South Wales, Australia, focusing on suburbs between the Port Kembla industrial complex and Lake Illawarra (the Warrawong area). MAIN OUTCOME MEASURES: Standardised incidence ratios (SIRs) for leukaemia; current measured and past estimated ambient air benzene concentrations; and expected leukaemia cases attributable to estimates of ambient air benzene concentrations. RESULTS: In 1989-1996, 12 leukaemia cases among Warrawong residents aged less than 50 years were observed, more than the 3.49 cases expected from the rate in the rest of the Illawarra region (SIR, 343.8; 99% CI, 141.6-691.7). These people lived in suburbs immediately to the south-southwest of a coke byproducts plant (a major industrial source of benzene, one of the few known leukaemogens). The greatest excess was among 15-24-year-olds (SIR, 1085.6; 99% CI, 234.1-3072.4). In 1996, ambient air concentrations of benzene averaged less than 1 part per billion (ppb). Since 1970, ambient air concentrations of benzene were estimated to have averaged up to 3 ppb, about one-thousandth of the level at which leukaemia risk has been identified in occupational epidemiological studies. Using the risk assessment model developed by the US Environmental Protection Agency, we estimate that past benzene levels in the Warrawong area could have resulted in 0.4 additional cases of leukaemia in 1989-1996. CONCLUSIONS: The excess occurrence of leukaemia in the Warrawong area in 1989-1996 is highly unusual. Current environmental benzene exposure and the reconstructed past environmental benzene exposure level are too low to explain the large excess of leukaemia. The cause of the cluster is uncertain.

Adolescent↗

Understanding the costs of ambulatory care training.

While patient care has been shifting to the ambulatory setting, the education of health care professionals has remained essentially hospital-based. One factor discouraging the movement of training into community-based ambulatory settings is the lack of understanding of what the costs of such training are and how these costs might be offset. The authors describe a model for ambulatory care training that makes it easier to generalize about to quantify its educational costs. Since ambulatory care training does not exist in a vacuum separate from inpatient education, the model is compatible with the way hospital-based education costs are derived. Thus, the model's elements can be integrated with comparable hospital-based training cost elements in a straightforward way to allow a total-costing approach. The model is built around two major sets of variables affecting cost. The first comprises three types of costs--direct, indirect, and infrastructure--and the second consists of factors related to the training site and factors related to the educational activities of the training. The model is constructed to show the various major ways these two sets of variables can influence training costs. With direct Medicare funding for some ambulatory-setting-based education pending, and with other regulatory and market dynamics already in play, it is important that educators, managers, and policymakers understand how costs, the characteristics of the training, and the characteristics of the setting interact. This model should assist them. Without generalizable cost estimates, realistic reimbursement policies and financial incentives cannot be formulated, either in the broad public policy context or in simple direct negotiations between sites and sponsors.

Ambulatory Care↗

Matrix metalloproteinase-9 maps to the distal end of chromosome 2 in the mouse.

The activity and expression of matrix metalloproteinase-9/gelatinase B (MMP-9), an enzyme implicated in the implantation process in mice, was investigated in normal and parthenogenetic blastocyst outgrowths. Conditioned media from parthenogenetic blastocysts after 4 days of culture had reduced levels of MMP-9 activity compared to conditioned medium from normal outgrowths. Levels of MMP-9 mRNA assayed by reverse transcription-polymerase chain reaction methods were also reduced in parthenogenetic blastocysts compared to normal outgrowths. Genetic mapping studies showed that Mmp9 maps to the distal end of chromosome 2 near the proximal boundary of a region affected by genomic imprinting. Both parental alleles of Mmp9, however, are expressed in 11.5-day embryos derived from interspecific crosses of Mus musculus and Mus spretus. Thus, loss of MMP-9 activity in parthenogenetic blastocysts does not appear to be due to imprinting but, rather, due to a defect of trophoblast giant cell proliferation and differentiation.

Animals↗

Expression of proteinases and proteinase inhibitors during embryo-uterine contact in the pig.

Implantation in pigs is noninvasive and characterized by interdigitation of embryonic and endometrial epithelial cell processes. However, when pig embryos are transferred to ectopic sites, trophoblast becomes invasive. The objective of this study was to evaluate expression of proteinases and proteinase inhibitors in pig embryos and uteri at the time of endometrial attachment. RNA was extracted from Day 15.75 pig embryos and uteri and reverse transcribed, and cDNA was amplified by polymerase chain reactions using primers specific for urokinase-type plasminogen activator (uPA), matrix metalloproteinases-2 and -9 (MMP-2 and -9), and tissue inhibitors of MMP-1, -2, and -3 (TIMP-1, -2, and -3). Localization of transcripts for the genes of interest in embryos and uteri was performed using in situ hybridization with antisense riboprobes. Day 15.75 pig embryos and uteri expressed transcripts for uPA, MMP-2 and -9, and TIMP-1, -2, and -3. In situ hybridization revealed weak expression of uPA in the trophectoderm and moderate expression in the adjacent extraembryonic endoderm. TIMP-1 transcripts were abundant in extraembryonic endoderm and scattered throughout the trophectoderm. TIMP-2 appeared to be expressed in all cells of the embryo. TIMP-3 expression was observed in the trophectoderm and, to a lesser extent, in the extraembryonic endoderm. Specific localization of MMP-2 and -9 transcripts above background was not observed by in situ hybridization in either embryos or uterus. Uterine expression of uPA and TIMP-1, -2 and -3 was localized to the endometrial stroma. Transcripts of these genes were not observed in either the luminal or glandular endometrial epithelium. These results suggest that pig embryos and uteri express a wide array of proteinases and proteinase inhibitors during the period of uterine association. The abundant expression of proteinases and proteinase inhibitors during the period of uterine association. The abundant expression of TIMP in pig embryos may partially explain the absence of invasive implantation in this species in contrast to implantation typified by rodents and primates.

Animals↗

Implant outcomes: towards a mixed methodology for evaluating the efficacy of adult cochlear implant programmes.

Studies concerned with the efficacy of cochlear implants have traditionally focused on measuring enhancements in speech perception associated with implantation. This paper reports the findings of a study concerned with qualitative and quantitative measures of psychosocial benefit associated with the adult cochlear implant programme. Cochlear implants enhanced implantees' interpersonal communication skills and social confidence, and were associated with a reduction in the user's social anxiety. Broader socioeconomic gains were not achieved by implantees, mainly because of an absence of adequate employment and community education programmes associated with implant programmes.

Adult↗

Evaluating and improving the cost-effectiveness of the implantable cardioverter-defibrillator.

The implantable cardioverter defibrillator (ICD) is an expensive, widely used device for severe ventricular arrhythmias. Marginal cost-effectiveness analysis is a technique to examine the incremental cost of treatment strategy in relation to its effectiveness. In this study, we used this technique to analyze the cost-effectiveness of the ICD compared with that of electrophysiology (EP)-guided drug therapy and examined ways in which it may be improved. We analyzed Michigan Medicare discharge abstracts (1989 to 1992) and local physician visit, test, and ICD charges. Effectiveness was from 218 previously described patients with ICDs in whom the time of first event (first appropriate shock or death) was determined and presumed to represent "control" (EP-guided drug therapy) mortality. We assumed a 4-year life cycle for the ICD generator and 3.4% operative mortality and used a 5% discount to prevent value. Data were analyzed in a 1-month cycle Markov decision model over a 6-year horizon, and results were updated to 1993 dollars. ICD effectiveness was an increase in discounted mean life expectancy of 1.72 years. Cost-effectiveness was $31,100/year of life saved (YLS). Results were minimally or modestly sensitive to variations in preoperative mortality; resource use; consideration only of patients with ICDs who were receiving any antiarrhythmic drug or specifically amiodarone; and to a decrease in the percentage of first shocks that would equal death without the ICD until the assumed percentage decreased to < 38%. At ejection fraction of < 0.25 and > or = 0.25, cost-effectiveness was $44,000/YLS and $27,200/YLS, respectively, and without preimplant EP study was $18,100/ YLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗